Objective ·To investigate the role of interleukin-1β (IL-1β) in predicting the severity of oral and maxillofacial space infection (OMSI), and to explore the key mechanisms regulating IL-1β release, the critical immune cell subpopulations involved, and the intercellular communication networks among immune cells in OMSI patients. Methods ·A total of 62 OMSI patients admitted to the Department of Oral Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, from January to November 2023 were enrolled, including 20 patients with moderate infection, 21 with severe infection, and 21 with extremely severe infection. Logistic regression analysis was performed to identify risk factors for extremely severe infection, and receiver operating characteristic (ROC) curves were constructed to evaluate the ability of the above indicators to predict extremely severe infection. Peripheral blood mononuclear cells (PBMCs) from 2 patients in each group (moderate, severe and extremely severe) and 2 healthy controls (GSE224198) were analyzed using single-cell RNA sequencing (scRNA-seq) to identify key pro-inflammatory cell subtypes and genes, and to examine their changing trends with increasing infection severity. Cell-cell communication was assessed using CellChat. Quantitative real-time polymerase chain reaction (qPCR) and Western blotting were used to validate inflammasome activation levels in PBMCs. Results ·Compared with patients with moderate and severe infections, levels of procalcitonin (PCT) (P<0.05) and IL-1β (P<0.05) were significantly elevated in patients with extremely severe infection. Logistic regression identified IL-1β as an independent risk factor for extremely severe infection (OR=1.814, 95% CI 1.256‒2.621, P=0.002). The area under the ROC curve (AUC) for the combined prediction of extremely severe infection using IL-1β and PCT was 0.943. scRNA-seq revealed continuous upregulation of NLRP3 (NOD-like receptor family pyrin domain-containing 3) and IL1B gene expression in monocytes as infection severity increased, with intermediate monocytes being the main IL1B-expressing cell subtype. IL-1Β-IL-1R signaling, C-C motif chemokine ligand (CCL) and intercellular adhesion molecule (ICAM) signaling were significantly enhanced in monocytes. Macrophage migration inhibitory factor (MIF) signaling between T cells and monocytes also increased notably. With infection progression, the mRNA levels of NLRP3 and IL1B in peripheral blood rose steadily, and the protein levels of NLRP3, caspase-1 p20, apoptosis-associated speck-like protein containing a CARD (ASC) and IL-1β were persistently elevated. Conclusion ·The combined levels of IL-1β and PCT at admission can effectively predict extremely severe OMSI. NLRP3 inflammasome activation is observed in PBMCs of OMSI patients. The elevation of IL-1β is closely associated with intermediate monocytes. Monocyte-mediated IL-1Β-IL-1R, CCL and ICAM signaling pathways, along with T cell-mediated MIF signaling pathways, collectively promote the inflammatory response.